The current research proposal seeks to provide an improved estimate of cognitive decline associated with methamphetamine (MA) dependence by creating "discrepancy scores" which consist of the difference between expected cognitive performance and current performance on a cognitive battery. Expected cognitive performance will be estimated in MA-dependent and healthy control subjects using demographic variables, pre-morbid estimation procedures, and participants'school records prior to the initiation of drug abuse. We will then determine the neuroanatomical and behavioral predictors of discrepancy scores in MA-dependent subjects. Behavioral predictors will include drug abuse variables, demographic variables, and psychosocial factors, while neuroanatomical predictors will consist of gray matter and white matter measurements identified from automated and semi-automated analysis of structural MRI data (e.g., VBM and DTI). Identifying predictors of discrepancy scores will implicate risk factors for cognitive decline in MA dependence. The candidate has a background in clinical neuropsychology and he seeks two primary training goals from this award: 1) learn structural neuroimaging techniques, and 2) become an expert in substance abuse, particularly MA abuse. The candidate's work environment at the UCLA Laboratory of Molecular Neuroimaging provides an impeccable infrastructure for being trained in neuroimaging and substance abuse, and he will be mentored and consulted by renowned experts in these areas. The lab has several grant-funded, ongoing studies in MA dependence with strong ties to the Brain Mapping Center and the inpatient General Clinical Research Center (GCRC). As part of training, the candidate will attend several courses and workshops in foundational neuroimaging topics (programming, statistics, image acquisition, neuroanatomy) and more advanced neuroimaging topics (e.g., DTI interpretation), as well as courses in the biological and psychiatric bases of substance abuse. He will also attend annual conferences in substance abuse (CPDD) and neuroimaging (e.g., Human Brain Mapping), and meet with mentors regularly. The candidate plans to submit for a R01 grant toward the end of the award period. Long term, he plans to found an independent research career examining the relationship between brain structure and behavior in substance abuse. PUBLIC HEALTH RELEVANCE: Individuals who are dependent on methamphetamine (MA) have been found to have cognitive difficulties, but the extent to which these difficulties are attributable to MA consumption is unclear. The current project seeks to improve the measurement of cognitive decline associated with MA dependence, and identify risk factors for this decline. Knowledge of risk factors for cognitive decline can be used to assist prevention and treatment efforts.